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[18F]FDG PET-MRI provides survival biomarkers in primary central nervous system lymphoma in the elderly: an ancillary study from the BLOCAGE trial of the LOC network

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European Journal of Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Purpose

Primary central nervous system lymphoma (PCNSL) incidence is rising among elderly patients, presenting challenges due to poor prognosis and treatment-related toxicity risks. This study explores the potential of combining [18F]fluorodeoxyglucose ([18F]FDG) PET scans and multimodal MRI for improving management in elderly patients with de novo PCNSL.

Methods

Immunocompetent patients over 60 years with de novo PCNSL were prospectively enrolled in a multicentric study between January 2016 and April 2021. Patients underwent brain [18F]FDG PET-MRI before receiving high-dose methotrexate-based chemotherapy. Relationships between extracted PET (metabolic tumor volume (MTV), sum of MTV for up to five lesions (sumMTV), metabolic imaging lymphoma aggressiveness score (MILAS)) and MRI parameters (tumor contrast-enhancement size, cerebral blood volume (CBV), cerebral blood flow (CBF), apparent diffusion coefficient (ADC)) and treatment response and outcomes were analyzed.

Results

Of 54 newly diagnosed diffuse large B-cell PCNSL patients, 52 had positive PET and MRI with highly [18F]FDG-avid and contrast-enhanced disease (SUVmax: 27.7 [22.8–36]). High [18F]FDG uptake and metabolic volume were significantly associated with low ADCmean values and high CBF at baseline. Among patients, 69% achieved an objective response at the end of induction therapy, while 17 were progressive. Higher cerebellar SUVmean and lower sumMTV at diagnosis were significant predictors of complete response: 6.4 [5.7–7.7] vs 5.4 [4.5–6.6] (p = 0.04) and 5.5 [2.1–13.3] vs 15.9 [4.2–19.5] (p = 0.01), respectively. Two-year overall survival (OS) was 71%, with a median progression-free survival (PFS) of 29.6 months and a median follow-up of 37 months. Larger tumor volumes on PET or enhanced T1-weighted MRI were significant predictors of poorer OS, while a high MILAS score at diagnosis was associated with early death (< 1 year).

Conclusion

Baseline cerebellar metabolism and sumMTV may predict response to end of chemotherapy in PCNSL. Tumor volume and MILAS at baseline are strong prognostic factors.

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Data Availability

Original data will be made available upon reasonable request by e-mail.

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Acknowledgements

We would like to thank Dr. Inna Gertsenshteyn for proofreading our manuscript before submission. We would like to thank the Assistance publique—hôpitaux de Paris for the support given to this clinical study (PHRC LOCALYZE).

Author information

Author notes

  1. Khê Hoang-Xuan and Aurélie Kas contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine, Groupe Hospitalier Pitié-Salpêtrière, APHP, Sorbonne Université, Paris, France

    Laura Rozenblum, Philippe Naggara, Marine Soret, Valérie Causse-Lemercier & Aurélie Kas

  2. Sorbonne Université, INSERM, CNRS, Laboratoire d’Imagerie Biomédicale, LIB, Paris, France

    Laura Rozenblum, Damien Galanaud, Marine Soret & Aurélie Kas

  3. Department of Neuroradiology, Groupe Hospitalier Pitié-Salpêtrière, APHP, Sorbonne Université, Paris, France

    Damien Galanaud

  4. Deparrment of Neurology 2 Mazarin, APHP, Hôpitaux Universitaires La Pitié Salpêtrière - Charles Foix, Sorbonne Université, Inserm, CNRS, UMR S 1127, Institut du Cerveau, ICM, Paris, France

    Caroline Houillier & Khê Hoang-Xuan

  5. Department of Hematology, Institut Curie, Site Saint-Cloud and INSERM U932 Institut Curie, Université PSL, 75005, Paris, France

    Carole Soussain

  6. Department of Public Health, Sorbonne Université, INSERM, Institut Pierre Louis d’Epidémiologie Et de Santé Publique, AP-HP, Hôpitaux Universitaires Pitié-Salpêtrière - Charles Foix, Paris, France

    Amandine Baptiste & Lisa Belin

  7. Department of Nuclear Medicine, Institut Curie, St-Cloud, France

    Véronique Edeline

  8. Department of Hematology, Cochin Hospital, APHP, Paris, France

    Lise Willems

  9. Department of Hematology, Groupe Hospitalier Pitié-Salpêtrière, APHP, Sorbonne Université, Paris, France

    Sylvain Choquet

  10. Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Saint-Louis, Service de Neurologie, Paris, France

    Renata Ursu

Authors
  1. Laura Rozenblum
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  2. Damien Galanaud
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Contributions

Professors Kas and Galanaud, as well as Drs. Houilier, Rozenblum, V. Causse Lemercier, and M. Soret, contributed to the study’s conception and design. Dr. Rozenblum and Prof. Galanaud performed the MRI images data collection, while P. Naggara, Dr. Rozenblum, and Prof. Kas performed the PET images data collection. Drs. Soussain, Ursu, Willems, and Houillier, as well as Prof. Choquet and Hoang-Xuan, recruited the patients. A. Baptiste and L. Belin, in collaboration with Dr. Rozenblum, performed the statistical analysis. All authors reviewed and approved the final version of the manuscript.

Corresponding author

Correspondence to Laura Rozenblum.

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Ethics approval

The study was approved by the protection of persons committee (2014-002597-37) and the French National Agency for the Safety of Medicines and Health Products (ANSM), and abided by the principles of the Declaration of Helsinki.

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Informed consent was obtained from all individual participants included in the study.

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The authors affirm that human research participants provided informed consent for publication of the images in Fig. 2.

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The authors have no relevant financial or non-financial interests to disclose.

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Trial: LOCALYZE, NCT02313389, ancillary of phase III clinical trial BLOCAGE01 (Registered July 10, 2018 – retrospectively registered); https://clinicaltrials.gov/ct2/show/NCT03582254?term=LOCALYZE&draw=2&rank=1.

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Rozenblum, L., Galanaud, D., Houillier, C. et al. [18F]FDG PET-MRI provides survival biomarkers in primary central nervous system lymphoma in the elderly: an ancillary study from the BLOCAGE trial of the LOC network. Eur J Nucl Med Mol Imaging 50, 3684–3696 (2023). https://doi.org/10.1007/s00259-023-06334-w

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